Recherche clinique ville-hôpital, Méthodologies et Société
Présentation
L’équipe 7334 REMES (Recherche Clinique ville-hôpital, Méthodologies et Société) sous la direction du Pr Olivier Chassany a la particularité de regrouper des médecins de ville et des hôpitaux, autour de travaux de recherche clinique qui placent le patient au centre de la prise en charge et des décisions médicales le concernant.
- Le 1er axe de recherche de l’équipe dirigé par le Dr Martin Duracinsky analyse la qualité de vie des personnes en situation de pathologie et mesure leurs perceptions (« Patient-Centered Outcomes ») afin d’améliorer leur parcours de vie avec la maladie. Comment vivent-ils avec cette pathologie ? Supportent-ils les traitements associés ? Comment leur prise en charge pourrait être améliorée, facilitée ?...
- Le 2e axe de recherche est quant à lui destiné à améliorer le parcours de soins du patient avec pour ambition de jeter un pont entre la médecine de ville et l’hôpital. Cet axe est rendu possible par la mobilisation des médecins généralistes universitaires de Paris-Diderot et leur collaboration avec d’autres enseignants-chercheurs exerçant à l’hôpital. Du fait de sa spécificité, cet axe est sous la responsabilité de 2 chercheurs, le Pr Isabelle Mahé du côté hôpital et le Pr Jean-Pierre Aubert pour la ville.
Pour finir, les chercheurs de l’EA 7334 REMES travaillent sur deux autres axes.
- Dans le 3e axe, sous la responsabilité de la juriste Mihaela Matei, ils se demandent comment améliorer la législation qui encadre la recherche clinique, en intégrant la notion d’approche basée sur le risque (« risk-based approach »).
- Le 4e axe, confié à Philippe Lechat, concerne le développement d’outils électroniques d’aide à la prescription. Ce projet comporte notamment une recherche sur l’élaboration et la faisabilité des algorithmes nécessaires à la construction d’un logiciel permettant de vérifier la validité, la cohérence et l’adéquation d’une ordonnance médicale des médicaments prescrits pour un patient donné dans une indication thérapeutique définie.
Thèmes de recherche
Axe Patient-Centered Outcomes
Responsable : Dr Martin Duracinsky (duracinsky.m@gmail.com)
Axe Recherche clinique Ville-Hôpital
Responsables : Pr Isabelle Mahé (Isabelle.Mahe@lmr.aphp.fr) & Pr jean Pierre Aubert (docteur.aubert@gmail.com)
Axe Législation et recherche clinique
Responsable : Mihaela Matei
Axe Outils électroniques d’aide à la prescription
Responsable : Pr Philippe Lechat (philippe.lechat@drc.aphp.fr)
[hal-01874741] Quality of qualitative studies centred on patients in family practice: a systematic review
Date: 14 Sep 2018 - 16:52
Desc: [...]
[hal-01626865] Hémorragie du post-partum : recommandations pour la pratique clinique — Texte des recommandations (texte court)
Date: 31 Oct 2017 - 14:07
Desc: [...]
[hal-00750902] Significant correlation between a set of genetic polymorphisms and a functional brain network revealed by feature selection and sparse Partial Least Squares.
Date: 12 Nov 2012 - 16:24
Desc: Brain imaging is increasingly recognised as an intermediate phenotype to understand the complex path between genetics and behavioural or clinical phenotypes. In this context, a first goal is to propose methods to identify the part of genetic variability that explains some neuroimaging variability. Classical univariate approaches often ignore the potential joint effects that may exist between genes or the potential covariations between brain regions. In this paper, we propose instead to investigate an exploratory multivariate method in order to identify a set of Single Nucleotide Polymorphisms (SNPs) covarying with a set of neuroimaging phenotypes derived from functional Magnetic Resonance Imaging (fMRI). Recently, Partial Least Squares (PLS) regression or Canonical Correlation Analysis (CCA) have been proposed to analyse DNA and transcriptomics. Here, we propose to transpose this idea to the DNA vs. imaging context. However, in very high-dimensional settings like in imaging genetics studies, such multivariate methods may encounter overfitting issues. Thus we investigate the use of different strategies of regularisation and dimension reduction techniques combined with PLS or CCA to face the very high dimensionality of imaging genetics studies. We propose a comparison study of the different strategies on a simulated dataset first and then on a real dataset composed of 94 subjects, around 600,000 SNPs and 34 functional MRI lateralisation indexes computed from reading and speech comprehension contrast maps. We estimate the generalisability of the multivariate association with a cross-validation scheme and demonstrate the significance of this link, using a permutation procedure. Univariate selection appears to be necessary to reduce the dimensionality. However, the significant association uncovered by this two-step approach combining univariate filtering and L1-regularised PLS suggests that discovering meaningful genetic associations calls for a multivariate approach.
[hal-02342800] Noradrenergic neuronal development is impaired by mutation of the proneural HASH-1 gene in congenital central hypoventilation syndrome (Ondine's curse)
Date: 1 Nov 2019 - 12:45
Desc: Congenital central hypoventilation syndrome (CCHS, Ondine's curse) is a rare disorder of the chemical control of breathing. It is frequently associated with a broad spectrum of dysautonomic symptoms, suggesting the involvement of genes widely expressed in the autonomic nervous system. In particular, the HASH-1-PHOX2A-PHOX2B developmental cascade was proposed as a candidate pathway because it controls the development of neurons with a definitive or transient noradrenergic phenotype, upstream from the RET receptor tyrosine kinase and tyrosine hydroxylase. We recently showed that PHOX2B is the major CCHS locus, whose mutation accounts for 60% of cases. We also studied the proneural HASH-1 gene and identified a heterozygous nucleotide substitution in three CCHS patients. To analyze the functional consequences of HASH-1 mutations, we developed an in vitro model of noradrenergic differentiation in neuronal progenitors derived from the mouse vagal neural crest, reproducing in vitro the HASH-PHOX-RET pathway. All HASH-1 mutant alleles impaired noradrenergic neuronal development, when overexpressed from adenoviral constructs. Thus, HASH-1 mutations may contribute to the CCHS phenotype in rare cases, consistent with the view that the abnormal chemical control of breathing observed in CCHS patients is due to the impairment of noradrenergic neurons during early steps of brainstem development.
[hal-01740290] Four-days-a-week antiretroviral maintenance therapy in virologically controlled HIV-1-infected adults: the ANRS 162-4D trial
Date: 21 Mar 2018 - 17:50
Desc: Background: Intermittent treatment could improve the convenience, tolerability and cost of ART, as well as patients' quality of life. We conducted a 48 week multicentre study of a 4-days-a-week antiretroviral regimen in adults with controlled HIV-1-RNA plasma viral load (VL). Methods: Eligible patients were adults with VL < 50 copies/mL for at least 1 year on triple therapy with a ritonavir-boosted PI (PI/r) or an NNRTI. The study protocol consisted of the same regimen taken on four consecutive days per week followed by a 3 day drug interruption. The primary outcome was the proportion of participants remaining in the strategy with VL < 50 copies/mL up to week 48. The study was designed to show an observed success rate of > 90%, with a power of 87% and a 5% type 1 error. The study was registered with ClinicalTrials.gov (NCT02157311) and EudraCT (2014-000146-29). Results: One hundred patients (82 men), median age 47 years (IQR 40-53), were included. They had been receiving ART for a median of 5.1 (IQR 2.9-9.3) years and had a median CD4 cell count of 665 (IQR 543-829) cells/mm3. The ongoing regimen included PI/r in 29 cases and NNRTI in 71 cases. At 48 weeks, 96% of participants (95% CI 90%-98%) had no failure while remaining on the 4-days-a-week regimen. Virological failure occurred in three participants, who all resumed daily treatment and became resuppressed. One participant stopped the strategy. No severe treatment-related events occurred. Conclusions: Antiretroviral maintenance therapy 4 days a week was effective for 48 weeks in 96% of patients, leading to potential reduction of long-term toxicities, high adherence to the antiretroviral regimen and drug cost saving.
